DESCRIPTION: (Scanned from the Applicant's Description): Improvements in clinical management of immune rejection following organ transplantation have resulted in a steadily increasing demand for donor organs. Unfortunately, efforts to increase the supply of human organs available for transplantation have failed to keep pace with demand and appear unlikely to do so. Considerable research and development efforts have been devoted toward the use of animal organs, specifically those from pigs, as an innovative alternative to human organs. However, a number of xenotransplantation barriers need to be overcome prior to clinical use of pig organs. Genetic engineering of donor pigs, including generation of pigs with gene targeted modifications, will be necessary to overcome these barriers. A Phase II program is proposed to modify pigs for use in xenotransplantation, using homologous recombination to create both genetic knock-outs and knock-ins. Nuclear transfer technology, using donor fibroblast lines carrying the desired genetic modifications, will be used to generate the desired founder animals. PROPOSED COMMERCIAL APPLICATION: NOT AVAILABLE